Several environmental factors including food availability and ambient temperature can affect reproductive response to day length. Previous work demonstrated population-wide variation in the extent that individuals display seasonal reproductive adaptations. The general goal of the current proposal is to continue the discovery of the physiological mechanisms that underlie variation in reproductive responses to extrinsic factors both in the brain and in the testes of adult deer mice (Peromycus maniculatus). The proposed studies will determine if gonadal regression in response to short days or restricted food intake results from down-regulation of angiogenic factors which led to programmed cell death (apoptosis). Experiments will also determine the role of pineal melatonin in the mediation of angiogenesis during gonadal regression. During "spontaneous" gonadal recrudescence, we hypothesize that increased rates of vasculature remodeling and cellular growth, and reduced rates of programmed cell death will be observed, both in the testes and in the hypothalamic regions that regulate gonadal function. Other experiments will determine changes in expression of testicular genes during gonadal regression and redevelopment using cDNA microarrays, followed by Western analyses for products of putative regulatory genes. Microarray analyses will also be conducted to describe changes in the expression of brain genes during photoperiod-induced reproductive regression and photorefractoriness-induced gonadal development. Western blot analysis will then assess protein changes in the brain subsequent to up- and down-regulation of candidate "photoperiodism genes" at key points in the seasonal cycle. Taken together, these studies will apply molecular approaches to study ecologically-relevant features of reproductive function. The results of the proposed studies should provide a molecular basis for the variation in reproductive responses, as well as provide both formal and mechanistic information about reproductive regression and recrudescence in seasonally-breeding rodents.